(270 days)
The Elecsys Toxo IgM immunoassay is for the in vitro qualitative detection of IgM antibodies to Toxoplasma gondii in human serum and plasma. This assay may be used as an aid in the diagnosis of an acute or recent Toxoplasma gondii infection in suspected patients and pregnant women. Patient testing must be performed in conjunction with an anti-Toxoplasma gondii IgG antibody assay. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immuno-assay analyzers. This assay has not been cleared by the FDA for blood/plasma donor screening.
PreciControl Toxo IgM is used for quality control of the Elecsys Toxo IgM immunoassay on the Elecsys and cobas e immunoassay analyzers.
The Elecsys Toxo IgM is a two-step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. In the first incubation 10 uL of sample are automatically prediluted 1:20 with Elecsys Diluent Universal and T. gondii-specific recombinant antigen labeled with a ruthenium complex is added. Anti-Toxo IgM antibodies present in the sample react with the ruthenium-labeled T. gondii-specific recombinant antigen. Then biotinylated monoclonal human-IgM- specific antibodies and streptavidin-coated microparticles are added. The complex becomes bound to the solid phase via interaction of biotin and streptayidin. The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier. Results are determined automatically by the Elecsys software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by Toxo IgM calibration.
The provided document describes the Elecsys Toxo IgM Immunoassay, an in vitro qualitative test for the detection of IgM antibodies to Toxoplasma gondii. It details the performance evaluation supporting its substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and study proving the device meets them:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for substantial equivalence are not explicitly listed in a table format with numerical targets, as might be seen for a novel device. Instead, the document presents performance metrics and compares them to a predicate device and established CLSI protocols. The implicit acceptance criterion is that the Elecsys Toxo IgM assay demonstrates comparable performance (precision, reproducibility, and agreement with a predicate method for clinical samples) to the legally marketed predicate device, VIDAS TOXO IgM Test System (K923166), for its stated indications for use.
Below is a table summarizing the reported device performance:
| Performance Metric | Reported Device Performance (Elecsys Toxo IgM) |
|---|---|
| Precision | Repeatability (within-run): CV (%) range from 2.3% to 4.9% (Serum Pool 1 to 3).Intermediate Precision (within-lab): CV (%) range from 3.2% to 5.2% (PC Toxo IgM 1 to Serum Pool 3). |
| Reproducibility | Repeatability (within-site): CV (%) range from 1.9% to 4.0% (Serum Pool 1 to 3).Intermediate Precision (within-lab): CV (%) range from 3.6% to 4.6% (Serum Pool 2 to 3).Between Site: CV (%) range from 3.3% to 13.0% (Serum Pool 2 to 1).Total Precision: CV (%) range from 4.9% to 13.6% (Serum Pool 2 to 1). |
| Cross-reactivity | Tested 218 potentially cross-reacting samples. Most showed 0% cross-reactivity. Some observed cross-reactivity (Ama: 6.7%, EBV: 10%, HBV: 4.8%, Malaria: 8%, Rubella: 10%). Note: "Equivocal samples are counted as positive." |
| Matrix Equivalency | Evaluated serum/gel separation tubes, lithium heparin plasma, K2-EDTA plasma, and sodium citrate plasma. "All results met the acceptance criteria." (Specific criteria not detailed, but imply acceptable recovery compared to serum). |
| Hook Effect | "High-dose Hook effect does not lead to false-negative results." Demonstrated by diluting high-positive samples; results remained above the cutoff where expected. |
| Clinical Performance (Agreement with Predicate) | Study 1 (US Prospective, n=440):- Positive agreement: 66.7% (2/3)- Negative agreement: 98.6% (431/437)Study 2 (US Retrospective, n=60):- Positive agreement: NA (0/0)- Negative agreement: 98.3% (59/60)Study 3 (EU Prospective, General Population, n=101):- Positive agreement: 94.2% (81/86)- Negative agreement: 50.0% (7/14)Study 3 (EU Prospective, Pregnant Women, n=87):- Positive agreement: 93.2% (68/73)- Negative agreement: 53.9% (7/13) |
| Interference | Unaffected by high concentrations of Bilirubin, Hemoglobin, Intralipid, and Biotin (within specified limits). No interference from rheumatoid factors (up to 3720 IU/mL) or 18 common pharmaceuticals. Noted potential interference from unspecific IgM and, in rare cases, high titers of antibodies to immunological components, streptavidin or ruthenium. |
2. Sample Sizes Used for the Test Set and Data Provenance
The "test set" in this context refers to the clinical samples used for performance evaluation against the predicate device.
- Study 1: 440 prospective specimens from a US reference laboratory.
- Study 2: 60 retrospective samples from a US commercial sample vendor.
- Study 3: 101 prospective samples from the general population in Europe. (87 of these were pregnant women).
Data Provenance:
- Country of Origin: US (Study 1 & 2), Europe (Study 3).
- Retrospective/Prospective: Mix of prospective (Studies 1 & 3) and retrospective (Study 2) samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish the ground truth. The "ground truth" for the clinical performance studies (Studies 1, 2, and 3) was established by comparison with a "FDA cleared method," specifically the VIDAS TOXO IgM Test System (K923166), which served as the reference method. This indicates that the predicate device's results were considered the de-facto ground truth for the comparison.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method beyond comparing the Elecsys Toxo IgM results to those of the predicate device. It notes that "Equivocals are counted as discrepant results against the Elecsys." in the agreement calculations, implying a direct comparison without a multi-reader or independent adjudication process for discordant results.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
This is an in vitro diagnostic (IVD) assay, not an AI-assisted diagnostic imaging device or a decision support system for human readers. Therefore, an MRMC comparative effectiveness study involving human readers with and without AI assistance is not applicable to this type of device. The study evaluates the performance of the assay itself.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
Yes, the studies presented are essentially standalone performance evaluations of the Elecsys Toxo IgM immunoassay. It's an automated test run on Elecsys and cobas e immunoassay analyzers, with results determined automatically by its software. The performance data (precision, reproducibility, cross-reactivity, matrix equivalency, hook effect, and agreement with the predicate) are purely those of the assay system without human interpretation as part of the primary diagnostic step. Human involvement would be in sample collection and loading onto the analyzer, and clinical interpretation of the final report.
7. The Type of Ground Truth Used
The ground truth for the clinical performance evaluation was established by a predicate device/reference method: the VIDAS TOXO IgM Test System (K923166). In the context of IVD assays, this is a common and accepted form of "ground truth" for demonstrating substantial equivalence. It's not pathology, outcomes data, or expert consensus in the typical sense of a human panel reviewing images, but rather the result from another validated, cleared assay.
8. The Sample Size for the Training Set
The document does not provide information on a separate "training set" or its size for the Elecsys Toxo IgM immunoassay. For IVD assays like this, the "training" (or development/optimization) phase involves extensive analytical studies (e.g., reagent formulation, calibration curve development, cutoff determination, specificity, sensitivity studies during R&D) rather than machine learning on a distinct training dataset. The established "Assay Cut-off" was likely derived from a large set of characterized samples during the development phase.
9. How the Ground Truth for the Training Set Was Established
Since there isn't an explicit "training set" described in the context of machine learning, the concept of establishing ground truth for it doesn't directly apply. However, the document states:
"The cut-off for the Elecsys Toxo IgM immunoassay was established by the use of sample collectives characterized with commercially available assays."
This indicates that the cutoff was determined based on a large collection of samples whose Toxoplasma gondii IgM status was characterized using other commercially available (presumably well-established reference or predicate) assays. This process is analogous to establishing ground truth for a development or training phase in IVD contexts. Specific details on the number of samples or the exact methodology of "characterization" are not provided but it implies a reference method was used.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 23, 2017
ROCHE DIAGNOSTICS KELLI TÜRNER REGULATORY AFFAIRS PRINCIPAL 9115 HAGUE RD. INDIANAPOLIS IN 46250
Re: K162678
Trade/Device Name: Elecsys Toxo IgM. Elecsys Toxo IgM PreciControl Regulation Number: 21 CFR 866.3780 Regulation Name: Toxoplasma gondii serological reagents Regulatory Class: II Product Code: LGD, JJX Dated: May 19, 2017 Received: May 22, 2017
Dear Ms. Turner:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Ribhi Shawar -S For
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K162678
Device Name Elecsys Toxo IgM Immunoassay
Indications for Use (Describe)
Elecsys Toxo IgM Immunoassay
The Elecsys Toxo IgM immunoassay is for the in vitro qualitative detection of IgM antibodies to Toxoplasma gondii in human serum and plasma. This assay may be used as an aid in the diagnosis of an acute or recent Toxoplasma gondii infection in suspected patients and pregnant women. Patient testing must be performed in conjunction with an anti-Toxoplasma gondii IgG antibody assay.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immuno-assay analyzers. This assay has not been cleared by the FDA for blood/plasma donor screening.
PreciControl Toxo IgM
PreciControl Toxo IgM is used for quality control of the Elecsys Toxo IgM immunoassay on the Elecsys and cobas e immunoassay analyzers.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Elecsys Toxo IgM 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague RoadIndianapolis, IN 46250 |
| Contact | Kelli TurnerPhone: (317) 521-4515FAX: (317) 521-3080Email: kelli.turner@roche.com |
| Date Prepared | June 21, 2017 |
| Proprietary Name | 1) Elecsys Toxo IgM2) PreciControl Toxo IgM |
| Common Name | 1) Toxo IgM2) PreciControlToxo IgM |
| Classification Name | 1) Toxoplasma gondii serological reagents2) Single (specified) analyte controls (assayed and unassayed) |
| Product Codes | 1) LGD, 866.37802) JJX, 862.1660 |
| Predicate Device | 1) VIDAS TOXO IgM Test System (K923166) |
| Establishment Registration | Roche Diagnostics GmbH in Mannheim, Germany, is 9610126Roche Diagnostics GmbH in Penzberg, Germany, is 9610529Roche Diagnostics in the United States is 1823260 |
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1. DEVICE DESCRIPTION
The Elecsys Toxo IgM is a two-step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. In the first incubation10 uL of sample are automatically prediluted 1:20 with Elecsys Diluent Universal and T. gondii-specific recombinant antigen labeled with a ruthenium complex is added. Anti-Toxo IgM antibodies present in the sample react with the ruthenium-labeled T. gondii-specific recombinant antigen. Then biotinylated monoclonal human-IgM- specific antibodies and streptavidin-coated microparticles are added. The complex becomes bound to the solid phase via interaction of biotin and streptayidin. The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier. Results are determined automatically by the Elecsys software by comparing the electrochemiluminescence signal obtained from the reaction product of the sample with the signal of the cutoff value previously obtained by Toxo IgM calibration.
Reagents 1.1.
The reagent working solutions include:
- rackpack (kit placed on instrument)
- Streptavidin coated microparticles, -
- Reagent 1 (Toxoplasma-Ag~ Ru(bpy)2+3) and -
- Reagent 2 (Anti human IgM Ab~biotin). -
- Included with the kit: -
- . Calibrator 1 (negative calibrator) Human serum non-reactive for anti Toxo IgM
- . Calibrator 2 (positive calibrator) Human serum reactive for anti Toxo IgM
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1.2. Control
PreciControl Toxo IgM is a ready for use control serum based on human serum. The controls are used for monitoring the accuracy of the Elecsys Toxo IgM immunoassay.
The PreciControl Toxo IgM includes:
- PC Toxo IgM 1 (Human serum negative for Toxo IgM antibodies, preservatives) .
- PC Toxo IgM 2 (Human serum positive for Toxo IgM antibodies, preservatives) .
2. INDICATIONS FOR USE
The Elecsys Toxo IgM immunoasay is for the in vitro qualitative detection of IgM antibodies to Toxoplasma gondii in human serum and plasma. This assay may be used as an aid in the diagnosis of an acute or recent Toxoplasma gondii infection in suspected patients and pregnant women. Patient testing must be performed in conjunction with an anti-Toxoplasma gondii IgG antibody assay. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers. This assay has not been cleared by the FDA for blood/plasma donor screening.
Comparison with the predicate device
The Elecsys Toxo IgM immunoasay was compared to a commercially marketed kit VIDAS TOXO IgM Test System (K923166) by Biomerieux. Both kits have the same intended use and use the same methodology. Below are tables comparing the reagents and the procedures of the two devices.
| Similarities | ||
|---|---|---|
| Item | Device | Predicate |
| Intended Use | The Elecsys Toxo IgMimmunoassay is for the invitro qualitative detection ofIgM antibodies toToxoplasma gondii in humanserum and plasma. Thisassay may be used as an aidin the diagnosis of an acuteor recent Toxoplasma gondii | The VIDAS® TOXO IgM(TXM) assay is intendedfor use with a VJDAS®(Vitek ImmunoDiagnosticAssay System) instrumentas an automated enzyme-linked fluorescentimmunoassay (ELFA) forthe presumptive qualitative |
| Similarities | ||
| Item | Device | Predicate |
| infection in suspectedpatients and pregnantwomen. Patient testing mustbe performed in conjunctionwith an anti- Toxoplasmagondii IgG antibody assay.Theelectrochemiluminescenceimmunoassay “ECLIA” isintended for use on Elecsysand cobas e immuno-assayanalyzers. This assay has notbeen cleared by the FDA forblood/plasma donorscreening.PreciControl Toxo IgM isused for quality control ofthe Elecsys Toxo IgMimmunoassay on the Elecsysand cobas e immunoassayanalyzers. | detection of anti-Toxoplasma gondii IgMantibodies in human serum,as an aid in the diagnosis ofacute, recent, or reactivatedToxoplasma gondiiinfection. This assay mustbe performed inconjunction with an anti-Toxoplasma gondii IgGantibody assay. VIDASTXM assay performancehas not been established forprenatal screening ornewborn testing. This assayhas not been cleared by theFDA for blood/plasmadonor screening. | |
| Calibrator | Included with the kit | Same |
| Assay type | Sandwich ELISA | Same |
| Instrument Platform | Fully automated system | Same |
| Differences | ||
| Item | Device | Predicate |
| Assay Protocol | ElectrochemiluminescenceImmunoassay (ECLIA) | Enzyme-linked fluorescentimmunoassay (ELFA) |
| Sample type | Serum, lithium heparinplasma, potassium EDTAplasma and sodium citrateplasma | Serum |
| Calibrators | Two | One |
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NON-CLINICAL PERFORMANCE EVALUATION 3.
3.1. Precision
Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.
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Precision was determined at one site using Elecsys reagents, human sera and controls in a modified protocol (EP5-A) of the CLSI (Clinical and Laboratory Standards Institute): 6 times daily for 10 days (n = 60). The following results were obtained:
| Repeatability | Between-run | Intermediateprecision | ||||||
|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean [s/co] | SD [s/co] | CV (%) | SD [s/co] | CV (%) | SD [s/co] | CV (%) |
| PCd) Toxo IgM 1 | 60 | 0.146 | 0.004 | 2.5 | 0.003 | 1.9 | 0.005 | 3.2 |
| PC Toxo IgM 2 | 60 | 1.61 | 0.037 | 2.3 | 0.045 | 2.8 | 0.059 | 3.6 |
| Serum Pool 1 | 60 | 0.147 | 0.003 | 2.3 | 0.005 | 3.1 | 0.006 | 3.9 |
| Serum Pool 2 | 60 | 2.06 | 0.075 | 3.7 | 0.031 | 1.5 | 0.082 | 4.0 |
| Serum Pool 3 | 60 | 3.49 | 0.173 | 4.9 | 0.060 | 1.7 | 0.183 | 5.2 |
d) PC = PreciControl
Note: intermediate precision is within lab precision data.
Reproducibility 3.2.
Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.
Reproducibility was determined at two sites using Elecsys reagents and human sera in a modified protocol (EP5-A) of the CLSI (Clinical and Laboratory Standards Institute): 6 times daily for 10 days at each site (n = 120). The following results were obtained:
| Repeatability | Between-run | Intermediate precision | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean [s/co] | SD [s/co] | CV (%) | SD [s/co] | CV (%) | SD [s/co] | CV (%) | ||
| Serum Pool 1 | 120 | 0.161 | 0.003 | 1.9 | 0.006 | 3.5 | 0.006 | 4.0 | ||
| Serum Pool 2 | 120 | 2.01 | 0.065 | 3.3 | 0.03 | 1.5 | 0.072 | 3.6 | ||
| Serum Pool 3 | 120 | 3.37 | 0.135 | 4.0 | 0.073 | 2.2 | 0.153 | 4.6 | ||
| Between site | Total precision | |||||||||
| Sample | N | Mean [s/co] | SD [s/co] | CV (%) | SD [s/co] | CV (%) | ||||
| Serum Pool 1 | 120 | 0.161 | 0.021 | 13.0 | 0.022 | 13.6 | ||||
| Serum Pool 2 | 120 | 2.01 | 0.067 | 3.3 | 0.098 | 4.9 | ||||
| Serum Pool 3 | 120 | 3.37 | 0.174 | 5.2 | 0.232 | 6.9 |
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3.3. Cross-reactivity
| A total of 218 potentially cross-reacting samples were collected and tested with the Elecsys Toxo IgM | |
|---|---|
| assay. The results are shown in the table below. |
| Antibody or DiseaseState | # Tested | Elecsys Toxo IgMPositive | % Cross-reactivity |
|---|---|---|---|
| AMA | 15 | 1 | 6.7 |
| ANA | 26 | 0 | 0 |
| Chlamydia | 5 | 0 | 0 |
| CMV | 13 | 0 | 0 |
| EBV | 10 | 1 | 10 |
| Gonorrhea | 5 | 0 | 0 |
| HAV | 10 | 0 | 0 |
| HBV* | 21 | 0* | 4.8 |
| HCV | 12 | 0 | 0 |
| HIV | 13 | 0 | 0 |
| HSV | 9 | 0 | 0 |
| Influenza | 16 | 0 | 0 |
| Malaria* | 25 | 1* | 8 |
| Parvo B19 | 11 | 0 | 0 |
| Rubella* | 10 | 0* | 10 |
| Syphilis | 5 | 0 | 0 |
| TPHA | 4 | 0 | 0 |
| VZV | 8 | 0 | 0 |
*contains 1 HBV sample repeatedly equivocal by Elecsys and negative with reference, 1 Malaria sample repeatedly equivocal by Elecsys and positive with reference, 1 Rubella sample reactive in Elecsys and initially equivocal with reference (no repetition possible due to low sample volume). Equivocal samples are counted as positive.
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3.4. Matrix equivalency study
Studies were conducted to evaluate the suitability of the following 5 types of blood collectin tubes: serum/gel separation tubes, lithium heparin plasma. K2-EDTA plasma and sodium citrate plasma. A minimum of 49 sample pairs were drawn into serum and plasma collection tubes. The recovery of the analyte in the presence of the anti coagulant was compared to serum. All results met the acceptance criteria.
Limitations - interference 3.5.
The assay is unaffected by:
| Compound | Concentration |
|---|---|
| Bilirubin | < 684 µmol/L or < 40 mg/dL |
| Hemoglobin | < 1.24 mmol/L or < 2 g/dL |
| Intralipid | < 2000 mg/dL |
| Biotin | < 246 nmol/L or < 60 ng/mL |
Criterion: Samples ≤ 0.5 COI*: recovery within ± 0.25 COI and Samples > 0.5 COI recovery ± 20 %.
Samples should not be taken from patients receiving therapy with high biotin doses (i.e. >5 mg/day) until at least 8 hours following the last biotin administration.
No interference was observed from rheumatoid factors up to a concentration of 3720 IU/mL. The high-dose hook effect does not lead to false-negative results in the Elecsys Toxo IgM assay. In vitro tests were performed on 18 commonly used pharmaceuticals and in addition on spiramycine, sulfadiazine, folinic acid and pyrimethamine. No interference with the assay was found.
As with many u-capture assays an interference with unspecific IgM is observed. Increasing amounts of unspecific IgM may lead to a decrease in the recovery of positive samples with the Elecsys Toxo IgM assay.
In rare cases, interference due to extremely high titers of antibodies to immunological components, streptavidin or ruthenium can occur. These effects are minimized by suitable test design.
For diagnostic purposes, the results should always be assessed in conjunction with the patient's medical history, clinical examination and other findings.
*COI= cut off index
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3.6. Hook Effect
For verification of this claim and due to the fact that spiking of the analyte is not possible, three high positive serum samples (single donors), with a COI value of 30.5, 31.9 and 64.5 COI, (based on the measured Elecsys Toxo IgM result) were used for this experiment. It was diluted with native human negative serum in decreasing gradients. All dilution steps were measured in three-fold determination. The median of the signals for each dilution is calculated and, in relation to the dilution factor shown for each dilution in a diagram.
Acceptance criterion: For the Elecsys Toxo IgM assay it is claimed that High-dose Hook effect does not lead to false-negative results
Assay Cut-off 3.7.
The cut-off for the Elecsys Toxo IgM immunoassay was established by the use of sample collectives characterized with commercially available assays.
The classification of samples, based on the cut-off establishment, verification, and validation, is as follows:
- Sample results < 0.8 COI = Non-reactive sample .
- Sample results ≥ 0.8 to < 1.0 COI = Indeterminate (Border) sample .
- Sample results > 1.0 COI = Reactive sample .
CLINICAL PERFORMANCE EVALUATION 4.
Summary of clinical performance
To characterize the performance of the Elecsys Toxo IgM immunoassay, relative to an FDA cleared method, multicenter studies in US and EU were performed. In total, 601 samples were tested as detailed below.
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4.1. Study 1
A total of 440 prospective specimens were obtained from US reference laboratory. All specimens represented samples for whom anti Toxo testing had been ordered per clinical routine. The patient population consisted of 162 males and 278 females. There were 158 pregnant women among the females. The patient's age ranged from 2 to 86. The performance of the Elecsys Toxo IgM immunoassay, relative to an FDA cleared method is presented in the table below.
| Reference Toxo IgM Method | |||||
|---|---|---|---|---|---|
| ElecsysToxo IgM | Positive | Equivocal | Negative | Total | |
| Reactive | 2 | 0 | 2 | 4 | |
| Equivocal | 0 | 0 | 4 | 4 | |
| Non-reactive | 0 | 1 | 431 | 432 | |
| Total | 2 | 1 | 437 | 440 |
US prospectively collected overall patient population
| Agreement Classification | Numerator/Denominator | PercentAgreement | 95 % ConfidenceInterval |
|---|---|---|---|
| Positive agreement | 2/3 | 66.7 | 9.43 - 99.2 |
| Negative agreement | 431/437 | 98.6 | 97.0 - 99.5 |
Equivocals are counted as discrepant results against the Elecsys.
4.2. Study 2
A total of 60 retrospective samples were obtained from a US commercial sample vendor. The patient population consisted of 4 males and 56 females. There were 50 pregnant women among the females. All specimens represented samples from whom anti-Toxo testing had been ordered per clinical routine. The performance of the Elecsys Toxo IgM immunoassay, relative to an FDA cleared method is presented in the table below.
US retrospectively collected overall patient population
| Reference Toxo IgM Method | |
|---|---|
| --------------------------- | -- |
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| ElecsysToxo IgM | Positive | Equivocal | Negative | Total | |
|---|---|---|---|---|---|
| Reactive | 0 | 0 | 0 | 0 | |
| Equivocal | 0 | 0 | 1 | 1 | |
| Non-reactive | 0 | 0 | 59 | 59 | |
| Total | 0 | 0 | 60 | 60 |
| Agreement Classification | Numerator/Denominator | PercentAgreement | 95 % ConfidenceInterval |
|---|---|---|---|
| Positive agreement | 0/0 | NA | NA |
| Negative agreement | 59/60 | 98.3 | 91.1 - 100 |
4.3. Study 3
One hundred one (101) samples collected prospectively were obtained from the general population in Europe under suspicion of Toxoplasmosis consisting of 5 males and 96 females with an age range of 22 to 69. The agreement results are shown below.
EU prospectively collected overall patient population
| Reference Toxo IgM Method | |||||
|---|---|---|---|---|---|
| ElecsysToxo IgM | Positive | Equivocal | Negative | Total | |
| Reactive | 81 | 1 | 5 | 87 | |
| Equivocal | 0 | 1 | 1 | 2 | |
| Non-reactive | 4 | 1 | 7 | 12 | |
| Total | 85 | 3 | 13 | 101 |
| Agreement Classification | Numerator/Denominator | PercentAgreement | 95 % ConfidenceInterval |
|---|---|---|---|
| Positive agreement | 81/86 | 94.2 | 87.0 - 98.1 |
| Negative agreement | 7/14 | 50.0 | 23.0 - 77.0 |
{13}------------------------------------------------
Equivocals are counted as discrepant results against the Elecsys. In case of unanimously equivocal samples, samples will not be considered for agreement calculation.
Of the 101 prospectively collected European specimens described above, 87 were from pregnant women. The agreement results are shown below.
| Reference Toxo IgM Method | |||||
|---|---|---|---|---|---|
| ElecsysToxo IgM | Positive | Equivocal | Negative | Total | |
| Reactive | 68 | 0 | 5 | 73 | |
| Equivocal | 0 | 1 | 1 | 2 | |
| Non-reactive | 4 | 1 | 7 | 12 | |
| Total | 72 | 2 | 13 | 87 |
EU prospectively collected pregnant women
| Agreement Classification | Numerator/Denominator | PercentAgreement | 95 % ConfidenceInterval |
|---|---|---|---|
| Positive agreement | 68/73 | 93.2 | 84.7 - 97.7 |
| Negative agreement | 7/13 | 53.9 | 25.1 - 80.8 |
Equivocals are counted as discrepant results against the Elecsys. In case of unanimously equivocal samples, samples will not be considered for agreement calculation.
CONCLUSIONS 5.
The information provided in this Premarket Notification [510(k)] shows that the device Elecsys Toxo IgM is safe and effective and will support a substantial equivalence determination to the predicate device, VIDAS TOXO IgM Test System (K923166).
§ 866.3780
Toxoplasma gondii serological reagents.(a)
Identification. Toxoplasma gondii serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toToxoplasma gondii in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyToxoplasma gondii from clinical specimens. The identification aids in the diagnosis of toxoplasmosis caused by the parasitic protozoanToxoplasma gondii and provides epidemiological information on this disease. Congenital toxoplasmosis is characterized by lesions of the central nervous system, which if undetected and untreated may lead to brain defects, blindness, and death of an unborn fetus. The disease is characterized in children by inflammation of the brain and spinal cord.(b)
Classification. Class II (performance standards).